Hair regrowth in a patient with alopecia universalis and psoriasis vulgaris during deucravacitinib therapy

Abstract

Dear Editors,

Alopecia areata (AA) is an autoimmune disease characterized by non-scarring, hairless patches.¹ In alopecia universalis (AU), the most extensive and difficult-to-treat form,² hair loss occurs over the entire integument. It is estimated that the risk of developing AA is about 2.71 times higher in patients with psoriasis than in healthy patients.³ We report on a patient with psoriasis and AU who experienced hair regrowth on systemic therapy with deucravacitinib.

A 51-year-old man of European origin presented with almost complete hair loss, a state that had persisted for about 7 months, and an 18-year history of psoriasis vulgaris that had been insufficiently controlled under topical therapy (Psoriasis Area and Severity Index [PASI] = 8). There were no comorbidities, and the patient was not taking any long-term medication. The hair loss had initially begun in the beard area and then spread to the hairy scalp. Over the course of 4 weeks, all body hair had then fallen out (Figure 1a–c). The diagnosis of alopecia universalis was made on the basis of the clinical picture. The manifestation of AA was not associated with an acute worsening of psoriasis. No improvement was seen with topical pimecrolimus and corticosteroids on the scalp and eyebrows. The Severity of Alopecia Tool Score (SALT score) was 97 out of 100 and the Dermatology Life Quality Index (DLQI) was 19 out of 30.

We treated the psoriasis vulgaris as approved with the tyrosine kinase-2-inhibitor (TYK2-I) deucravacitinib (6 mg/d). The psoriatic skin lesions improved significantly within 3 months (PASI = 4). Furthermore, the eyebrows grew, followed by body and scalp hair. On the first follow-up visit after six weeks, isolated white hairs about 1 cm long were already visible on the scalp and eyebrows. In the further course, continuous hair growth occurred, so that after 7 months of therapy with deucravacitinib, the hair had largely grown back and only a few bald spots remained on the back of the head and in the genital area (SALT score 13) (Figure 2a–c). No adverse events occurred. The DLQI improved to 3 out of 30.

Janus kinases (JAK) are a family of tyrosine kinases with the four members JAK1, 2, and 3 as well as TYK2. They transmit signals from various cytokine receptors intracellularly. JAK2 acts as a homodimer or heterodimer, whereas JAK1, JAK3, and TYK2 act exclusively as heterodimers. Deucravacitinib inhibits TYK2 allosterically and is the only Janus kinase inhibitor (JAK-I) approved for the treatment of psoriasis vulgaris.⁴ The focus of clinical studies in AA has so far been primarily on inhibitors of JAK1–3.⁵ JAK-I baricitinib, which inhibits JAK1 and JAK2 in particular, and ritlecitinib, a selective dual inhibitor of JAK3 and the TEC family of kinases, have now been approved for the oral treatment of severe AA.⁶ It has not yet been conclusively established which cytokine signaling pathway inhibited by JAK-I is responsible for the therapeutic response to AA. Type I interferons (IFN) and interleukin (IL)-15 may play a role, but IL-12- and IL-23-mediated processes may also be involved.^{5, 7} Tyrosine kinase 2 is involved in signal transduction of several cytokines such as IFN, IL-12 and IL-23, but not IL-15.

To the best of our knowledge, this is one of the first cases in which an AU as a severe form of AA was successfully treated with deucravacitinib, the only specific TYK2 inhibitor approved to date. Although we cannot rule out the possibility that the regrowth of hair was spontaneous, the close temporal relationship with deucravacitinib therapy, the extent of the regrowth, and the rather poor prognosis of AU argue against purely spontaneous regrowth. Given the favorable safety profile of deucravacitinib, we believe controlled studies to evaluate its effect on AA are warranted.

C.J. has no conflicts of interest to report. M.P.S. received consultancy or lecture fees or participated in studies by the following companies: AbbVie, Almirall, Biogen, BMS, Celltrion, Janssen, Leo, Lilly, Novartis, Scinai, UCB. R.M. received consultancy or lecture fees or participated in studies by the following companies: Abbvie, Allmirall, Biogen, Böhringer-Ingelheim, Celgene, Janssen-Cilag, Leo, Lilly, MSD SHARP & DOHME, Novartis, Pfizer and UCB.